Cytocidal effects of human fibroblasts on HeLa cells in vitro.

Cocultivation of human fibroblasts and HeLa cells in vitro leads to the development of specific patterns of growth. These patterns depend on the cell density and cell-cell ratio in the initial mixed inoculum. Human fibroblasts can cause extensive nuclear fragmentation and cellular disintegration of HeLa cells in vitro after coculture for periods longer than 10 days, without subculturing, and with medium replacement every 2 days. This phenomenon is preceded by directional locomotion of the fibroblastic population parallel to the edges of and around HeLa colonies and by overgrowth of both cell types at the border sites. A dense border is thus developed around the HeLa colonies. In the absence of refeeding every 2 days, HeLa cells can overgrow, pass the dense border and form a new zone. Refeeding at this stage can again cause the formation of a second concentric dense border around the HeLa zone. This phenomenon may represent an in vitro metaphor of the invasive property of neoplastic cells. It also points out, however, the importance of feeding for the activation of fibroblasts against HeLa cells.